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Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series

BACKGROUND: Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton’s tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF)...

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Autores principales: Yang, Chuanwei, Cui, Yong, Ren, Xiaohui, Li, Ming, Yu, Kefu, Shen, Shaoping, Jiang, Haihui, Li, Mingxiao, Zhang, Xiaokang, Zhao, Xuzhe, Zhu, Qinghui, Lin, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243261/
https://www.ncbi.nlm.nih.gov/pubmed/35785180
http://dx.doi.org/10.3389/fonc.2022.901797
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author Yang, Chuanwei
Cui, Yong
Ren, Xiaohui
Li, Ming
Yu, Kefu
Shen, Shaoping
Jiang, Haihui
Li, Mingxiao
Zhang, Xiaokang
Zhao, Xuzhe
Zhu, Qinghui
Lin, Song
author_facet Yang, Chuanwei
Cui, Yong
Ren, Xiaohui
Li, Ming
Yu, Kefu
Shen, Shaoping
Jiang, Haihui
Li, Mingxiao
Zhang, Xiaokang
Zhao, Xuzhe
Zhu, Qinghui
Lin, Song
author_sort Yang, Chuanwei
collection PubMed
description BACKGROUND: Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton’s tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF) concentration. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing combination therapy in patients with r/r PCNSL. METHODS: We retrospectively analyzed r/r PCNSL patients who received combination therapy with rituximab, high-dose methotrexate, temozolomide, orelabrutinib and lenalidomide, and further explored the relationship between the efficacy and genetic characteristics. RESULTS: A total of fifteen patients were included in this retrospective study. The overall response rate (ORR) was 86.7%, the complete remission (CR) rate was 73.3% and the disease control rate (DCR) was 93.3%. Among 13 responders, 9 patients are still receiving oral orelabrutinib and lenalidomide. The most common adverse event (AEs) was transaminase increase (66.7%). No grade 4 AE or drug-related death was reported. Genomic sequencing showed that patients who responded to orelabrutinib had abnormal NF-κB activation, while those who had no response were mainly enriched with transcriptional misregulation. Patients who had mutations in TLR, BCR, or NF-κB pathway achieved complete or partial response to the orelabrutinib-containing therapy. Moreover, the blood and cerebrospinal fluid circulating tumor DNA (ctDNA) were closely associated with tumor recurrence and treatment response and sustained tumor responses correlated with the clearance of ctDNA. CONCLUSION: Orelabrutinib-containing regimen was effective and well-tolerated in patients with r/r PCNSL. Genome sequencing of tumor samples could help to screen patients who may respond to the orelabrutinib-containing regimen, and liquid biopsy may contribute to tracing tumor burden and monitoring treatment response.
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spelling pubmed-92432612022-07-01 Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series Yang, Chuanwei Cui, Yong Ren, Xiaohui Li, Ming Yu, Kefu Shen, Shaoping Jiang, Haihui Li, Mingxiao Zhang, Xiaokang Zhao, Xuzhe Zhu, Qinghui Lin, Song Front Oncol Oncology BACKGROUND: Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton’s tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF) concentration. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing combination therapy in patients with r/r PCNSL. METHODS: We retrospectively analyzed r/r PCNSL patients who received combination therapy with rituximab, high-dose methotrexate, temozolomide, orelabrutinib and lenalidomide, and further explored the relationship between the efficacy and genetic characteristics. RESULTS: A total of fifteen patients were included in this retrospective study. The overall response rate (ORR) was 86.7%, the complete remission (CR) rate was 73.3% and the disease control rate (DCR) was 93.3%. Among 13 responders, 9 patients are still receiving oral orelabrutinib and lenalidomide. The most common adverse event (AEs) was transaminase increase (66.7%). No grade 4 AE or drug-related death was reported. Genomic sequencing showed that patients who responded to orelabrutinib had abnormal NF-κB activation, while those who had no response were mainly enriched with transcriptional misregulation. Patients who had mutations in TLR, BCR, or NF-κB pathway achieved complete or partial response to the orelabrutinib-containing therapy. Moreover, the blood and cerebrospinal fluid circulating tumor DNA (ctDNA) were closely associated with tumor recurrence and treatment response and sustained tumor responses correlated with the clearance of ctDNA. CONCLUSION: Orelabrutinib-containing regimen was effective and well-tolerated in patients with r/r PCNSL. Genome sequencing of tumor samples could help to screen patients who may respond to the orelabrutinib-containing regimen, and liquid biopsy may contribute to tracing tumor burden and monitoring treatment response. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243261/ /pubmed/35785180 http://dx.doi.org/10.3389/fonc.2022.901797 Text en Copyright © 2022 Yang, Cui, Ren, Li, Yu, Shen, Jiang, Li, Zhang, Zhao, Zhu and Lin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yang, Chuanwei
Cui, Yong
Ren, Xiaohui
Li, Ming
Yu, Kefu
Shen, Shaoping
Jiang, Haihui
Li, Mingxiao
Zhang, Xiaokang
Zhao, Xuzhe
Zhu, Qinghui
Lin, Song
Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
title Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
title_full Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
title_fullStr Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
title_full_unstemmed Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
title_short Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
title_sort orelabrutinib combined with lenalidomide and immunochemotherapy for relapsed/refractory primary central nervous system lymphoma: a retrospective analysis of case series
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243261/
https://www.ncbi.nlm.nih.gov/pubmed/35785180
http://dx.doi.org/10.3389/fonc.2022.901797
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